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Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma

Citation

Corona, G and Vaccher, E and Sandron, S and Sartor, I and Tirelli, U and Innocenti, F and Toffoli, G, Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma, Clinical Pharmacology and Therapeutics, 83, (4) pp. 601-606. ISSN 0009-9236 (2008) [Refereed Article]

Copyright Statement

Copyright 2008 American Society for Clinical Pharmacology and Therapeutics

DOI: doi:10.1038/sj.clpt.6100330

Abstract

The coadministration of protease inhibitors with anticancer drugs in the management of human immunodeficiency virus-related malignancies can cause potential drug–drug interactions. The effect of lopinavir/ritonavir (LPV/RTV) on the pharmacokinetics of irinotecan (CPT11) has been investigated in seven patients with Kaposi's sarcoma. Coadministration of LPV/RTV reduces the clearance of CPT11 by 47% (11.3±3.5 vs 21.3±6.3 l/h/m2, P=0.0008). This effect was associated with an 81% reduction (P=0.02) of the AUC (area under the curve) of the oxidized metabolite APC (7-ethyl-10-[4-N-(5-aminopentanoic-acid)-1-piperidino]-carbonyloxycamptothecin). The LPV/RTV treatment also inhibited the formation of SN38 glucuronide (SN38G), as shown by the 36% decrease in the SN38G/SN38 AUCs ratio (5.9±1.6 vs 9.2±2.6, P=0.002) consistent with UGT1A1 inhibition by LPV/RTV. This dual effect resulted in increased availability of CPT11 for SN38 conversion and reduced inactivation on SN38, leading to a 204% increase (P=0.0001) in SN38 AUC in the presence of LPV/RTV. The clinical consequences of these substantial pharmacokinetic changes should be investigated.

Item Details

Item Type:Refereed Article
Research Division:Chemical Sciences
Research Group:Analytical Chemistry
Research Field:Separation Science
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Sandron, S (Dr Sara Sandron)
ID Code:93931
Year Published:2008
Web of Science® Times Cited:25
Deposited By:Austn Centre for Research in Separation Science
Deposited On:2014-08-22
Last Modified:2014-08-27
Downloads:0

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